thrombolytics notes Thrombolytic therapy is the use of drugs to break up or dissolve blood clots, which are the main cause of both heart attacks and stroke.

1. THROMBOLYTICS
Thrombolytics or fibrinolytics
Definition :
 These drugs are used to breakdown of thrombin or clot to reanalyze including
blood vessels .
 There are curative rather than prophylactic work by activating the nature
fibrinolytic system.
 Venous thrombin are lysed more easily than arterial and recent thrombi respond
better :little effect on thrombin >3days old.
Mechanism:
Fibrinolytics examples :
Streptokinase ,urokinase ,alteplase,reteplase,tenecteplase.
Streptokinase:

2.  It is obtained from beta hemolytic Streptococcus Group C.
 It is inactive as such combines with circulating plasminogen to
form an active Complex which then causes limited proteolysis of
the Other plasminogen molecules to plasmin. It plasma half life is
estimated to be 30 to 80 minutes.
 Streptokinase is antigenic , can cause hypersensitivity reactions
and anaphylaxis, especially when used second time in a patient .
Repeated doses are also less effective due to neutralization by
antibodies. Fever is common , hypertension and arrhythmia are
reported.
Use:
It is least expensive and is still widely used in India and other developing
countries.
Dose :
 For Myocardial Infarction: 7.5to 15lac IU
 For deep venous thrombosis and pulmonary embolism : 2.5lac IU.
Urokinase :
 It is an enzyme isolated from human urine now prepared from
cultured human kidney cells which activates plasminogen directly
and has a plasma half life of 10 to 15 minutes.
 It is a non antigenic fever occurs during treatment but
hypotension and allergic phenomena are rare indicated in patients
in home streptokinase has been used for an earlier episode use has
now declined due to introduction of newer fibrinolytics.
Dose:
2.5lac to 10lac IU/vial.

3. Ateplase:
 It is also referred as tissue plasminogen activator which is
produced by Recombinant DNA technology from human tissue
culture is specifically activates gel face plasminogen already
bound to fibrin and has little action on circulating plasminogen.
 It is rapidly cleared by liver and has a plasma half life of 4to 8
minutes because of the short half life it needs to be given by slow
intravenous infusion and often requires heparin co-administration.
 It is known antigenic but nausea and mild hypotension and fever
may occur.
Dose:
50mg vial with 50ml water.
Reteplase :
 It is a modified rt-pa that is longer acting but somewhat less
specific for fibrin bound plasminogen .
 The longer duration of action enables Bolus dose administration .
Tenecteplase:
 It is a mutant variant of rtpa with higher fibrins selectivity and
longer duration of action.
Dose:
A single IV bolus dose of 0.5mg/kg.
Use of Thrombolytics:
1. Acute myocardial infarction :

4. Fibrinolytics are an alternative first-line approach to
emergency percutaneous coronary intervention with stent
placement.
2. Deep vein thrombosis:
Thrombolytics can decrease subsequent pain and
swelling in leg pelvis shoulder and up to 60%
patients can be successfully treated.
3. Pulmonary embolism:
Fibrinolytic therapy is indicated in large and life-
threatening pulmonary embolism.
4. Peripheral arterial occlusion :
fibrinolytics recanalize 40% Limb artery occlusion
especially those treated within 72 hours.
5. Stroke:
Used in the treatment of stroke.
Contraindications :
It is contraindicated in all situations where the risk of bleeding is
increased such as recent trauma surgery biopsies hemorrhagic stroke or
peptic ulcer.
Anti Fibrinolytics
These are the drugs which inhibit plasminogen activation and dissolution of clot.
Epsilon amino caproic acid (EACA) :
 It is an analogue of amino acid lysine combines with lysine
binding site of plasminogen and plasmin so it is unable to bind
fibrin and Lysine.

5.  It is a specific antidotes for fibrinolytic agent and has been used in
many hyper plasmin anemic states excessive intravascular
fibrinolysis resulting in bleeding.
 For example overdose of streptokinase or Uro kinase or ateplase
and to prevent re occurrence of subarachnoid and gastrointestinal
hemorrhage and certain traumatic and surgical bleedings .
Dose:
Tab0.5gm
Tranexaemic acid:
It binds to the Lysine binding site on plasminogen and prevents is combination with
fibrin and is 7 times more potent.
Use:
It is used in the prevention for excessive bleeding in overdose of fibrinolytics and after
cardio pulmonary bypass surgery.
Side effects :
Nausea ,diarrhoea, headache and thrombophlebitis.
Aprotinin:
It is a polypeptide isolated from bovine tissues with polyvalent serine protease inhibitory
activity.
Use:
It reduces blood loss in traumatic hemorrhagic and endotoxic shock.
Dose :
2-5lac KIU. .

6. Reference :
 KD Tripathi - textbook of essentials of medical Pharmacology 6th edition pg. no.
605-608.
 Thrombolytics haematology by med bullets.
Submitted by
P.Vara lakshmi
PharmD